The thesis of the original grant proposal was that a family of enzymes known as phosphoribosyltransferases (PRTases) divergently evolved from a common ancestral protein. This hypothesis was based on the striking similarities in the physical-chemical properties of these enzymes as well as the high incidence of structural gene mutations (with associated metabolic disorders) seen in the PRTases of man. These mutations were suggested to be an inherited consequence of the primordial PRTases' instability to mutation. To investigate this theory, the high resolution structures of 3 PRTases, quinolinate PRTase (from hog liver), hypoxanthine-guanine PRTase and adenine PRTase (from human red blood cells), were to be detemined by X-ray diffraction analysis and subsequently compared. Since high resolution native data had already been collected on quinolinate this past year has primarily focused on solving the structure of QPRTase. The major direction in the forthcoming year will be to successfully solve the structure at high resolution. Data from both a samarium and PHMB derivative will be utilized to obtain a multiple isomorphous-anomalous difference electron density map. HGPRTase continues to be in short supply but a crystallization survey will be continued using substrate molecules to stabilize the protein. Once the appropriate conditions have been found, an X-ray examination of the crystals will be initiated and data collected.